ZILPATEROL HYDROCHLORIDE

Comments:

ARfD of 0.04 μg/kg bw based on a LOAEL of 0.76 μg/kg bw for acute pharmacological effects observed in the single-dose human study.

MRL Comment:

The recommended MRLs for cattle are 3.3 μg/kg in kidney, 3.5 μg/kg in liver and 0.5 μg/kg in muscle.

Report: 

Residues: 

ADI:

0–0.04 µg/kg b.w.

Comments:

The Committee established an ADI of 0–0.04 µg/kg body weight on the basis of a LOAEL of 0.76 μg/kg body weight for tremor in humans. An uncertainty factor of 20 was applied, comprising a default uncertainty factor of 10 for human individual variability and an additional uncertainty factor of 2 to account for the use of a LOAEL for a slight effect instead of a NOAEL. The Committee noted that the ADI is based on an acute effect. The Committee also noted that the upper bound of the ADI provides a margin of safety of at least 1250 with respect to the NOAEL of 50 μg/kg body weight per day for the formation of leiomyomas in rats.

MRL Comment:

The Committee concluded that it was not possible to recommend MRLs for zilpaterol. The following data are needed to establish MRLs: • results from studies investigating marker residue in liver and kidney; • results from studies determining marker residue to total residue ratio in liver and kidney; • results from depletion studies to enable the derivation of MRLs compatible with the ADI. All such studies should use sufficiently sensitive validated analytical methods capable of measuring zilpaterol and its major metabolites in edible tissues of cattle.

Meeting:

78

Report: 

Tox Monograph: 

Residues: